Amoxycillin - a new antibiotic

1972 ◽  
Vol 10 (16) ◽  
pp. 61-62
Keyword(s):  
Antibacterial Activity ◽  
Hydroxyl Group ◽  
Cross Resistance ◽  
Side Chain

Amoxycillin (Amoxil) is a new penicillin which differs from ampicillin only in possessing a hydroxyl group on the side chain. In vitro the drugs have identical antibacterial activity and cross-resistance is complete.1 Nevertheless the manufacturers make only a cursory comparison between features of the two antibiotics in their promotional literature. This is a serious omission, since a new antibiotic should not be launched with so little reference to the yard-stick by which it will inevitably be assessed, namely the manner in which it compares with the well-tried ampicillin, over which it may have certain advantages. Bencard, which markets Amoxil is in fact a subsidiary of Beecham, the makers of ampicillin.

17α-HYDROXYLASE DEFICIENCY. A COMBINATION OF HYDROXYLATION DEFECT AND REVERSIBLE BLOCKADE IN ALDOSTERONE BIOSYNTHESIS

1979 ◽  
Vol 90 (3) ◽  
pp. 490-504 ◽  
Author(s):  
D. R. Rovner ◽  
J. W. Conn ◽  
E. L. Cohen ◽  
F. G. Berlinger ◽  
D. C. Kern ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Extracellular Fluid ◽  
Plasma Renin ◽  
Hydroxyl Group ◽  
Side Chain ◽  
Hydroxylase Deficiency ◽  
Resultant Increase

ABSTRACT We have studied the hormonal secretion and excretion patterns in a patient with the XX type of 17α-hydroxylase deficiency. In the untreated state, the patient's urine contained only those steroids which do not require 17-hydroxylation in their biosynthesis. Aldosterone was not produced in the patient and the metabolic product of its immediate precursor, 18-hydroxy-11-dehydro-tetrahydrocorticosterone, was excreted in markedly elevated amounts. This apparent complete block in 18 oxidation was reversible upon long-term ACTH suppression within 27 days. Direct in vitro incubation of the patient's adrenal gland removed at operation demonstrated, 1) the complete lack of 17α-hydroxylase activity, 2) the functional block in the ability to oxidize the hydroxyl group at the 18 methyl side chain. The addition of physiological concentrations of angiotensin to the incubation medium further showed, 3) angiotensin mildly stimulated the entire aldosterone biosynthetic pathway, 4) angiotensin directly stimulated the conversion of 18-hydroxycorticosterone to aldosterone. We propose that in this patient, 17-hydroxylase deficiency produced a decreased plasma concentration of cortisol, followed by stimulation of deoxycorticosterone production by ACTH. The resultant increase in extracellular fluid volume suppressed plasma renin activity. This resulted in a low plasma concentration of angiotensin II which directly suppressed oxidation of 18-hydroxycorticosterone to aldosterone. This defect has been called corticosterone methyl oxidase defect type 2.

scholarly journals In VitroAntibacterial Activity of AZD0914, a New Spiropyrimidinetrione DNA Gyrase/Topoisomerase Inhibitor with Potent Activity against Gram-Positive, Fastidious Gram-Negative, and Atypical Bacteria

2014 ◽  
Vol 59 (1) ◽  
pp. 467-474 ◽  
Author(s):  
Michael D. Huband ◽  
Patricia A. Bradford ◽  
Linda G. Otterson ◽  
Gregory S. Basarab ◽  
Amy C. Kutschke ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Legionella Pneumophila ◽  
Bacterial Species ◽  
Dna Gyrase ◽  
Cross Resistance ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Topoisomerase Inhibitor

ABSTRACTAZD0914 is a new spiropyrimidinetrione bacterial DNA gyrase/topoisomerase inhibitor with potentin vitroantibacterial activity against key Gram-positive (Staphylococcus aureus,Staphylococcus epidermidis,Streptococcus pneumoniae,Streptococcus pyogenes, andStreptococcus agalactiae), fastidious Gram-negative (Haemophilus influenzaeandNeisseria gonorrhoeae), atypical (Legionella pneumophila), and anaerobic (Clostridium difficile) bacterial species, including isolates with known resistance to fluoroquinolones. AZD0914 works via inhibition of DNA biosynthesis and accumulation of double-strand cleavages; this mechanism of inhibition differs from those of other marketed antibacterial compounds. AZD0914 stabilizes and arrests the cleaved covalent complex of gyrase with double-strand broken DNA under permissive conditions and thus blocks religation of the double-strand cleaved DNA to form fused circular DNA. Whereas this mechanism is similar to that seen with fluoroquinolones, it is mechanistically distinct. AZD0914 exhibited low frequencies of spontaneous resistance inS. aureus, and if mutants were obtained, the mutations mapped togyrB. Additionally, no cross-resistance was observed for AZD0914 against recent bacterial clinical isolates demonstrating resistance to fluoroquinolones or other drug classes, including macrolides, β-lactams, glycopeptides, and oxazolidinones. AZD0914 was bactericidal in both minimum bactericidal concentration andin vitrotime-kill studies. Inin vitrocheckerboard/synergy testing with 17 comparator antibacterials, only additivity/indifference was observed. The potentin vitroantibacterial activity (including activity against fluoroquinolone-resistant isolates), low frequency of resistance, lack of cross-resistance, and bactericidal activity of AZD0914 support its continued development.

scholarly journals Siderophore Cephalosporin Cefiderocol Utilizes Ferric Iron Transporter Systems for Antibacterial Activity againstPseudomonas aeruginosa

2016 ◽  
pp. AAC.01405-16 ◽  
Author(s):  
Akinobu Ito ◽  
Toru Nishikawa ◽  
Shuhei Matsumoto ◽  
Hidenori Yoshizawa ◽  
Takafumi Sato ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Ferric Iron ◽  
Side Chain ◽  
Hydroxyl Groups ◽  
Intracellular Accumulation ◽  
Chelating Activity ◽  
Transporter Systems ◽  
Chelating Complex ◽  
Catechol Moiety

Cefiderocol (S-649266) is a novel parenteral siderophore cephalosporin conjugated with a catechol moiety at the 3rd-position side chain. Thein vitroactivity of cefiderocol againstPseudomonas aeruginosawas enhanced in the iron-depleted condition where that of ceftazidime was not affected. The monitoring of [Thiazole-14C]-cefiderocol revealed the increased intracellular accumulation of cefiderocol in theP. aeruginosacells incubated under iron-depleted condition compared with those incubated under iron-sufficient condition. Cefiderocol was shown to have potent chelating activity with ferric iron, and extracellular iron was efficiently transported intoP. aeruginosacells in the presence of cefiderocol as well as siderophores, while enhanced transport of extracellular ferric iron was not observed when one of the hydroxyl groups of catechol moiety of cefiderocol was substituted with a methoxy group. We conclude that cefiderocol forms a chelating complex with iron, which is actively transported intoP. aeruginosacells via iron transporters, resulting in potent antibacterial activity of cefiderocol againstP. aeruginosa.

Incorporation of Fluorinated Pyridine in the Side Chain of 4-Aminoquinolines: Synthesis, Characterization and Antibacterial Activity

Drug Research ◽  
2017 ◽  
Vol 68 (01) ◽  
pp. 17-22 ◽  
Author(s):  
Reza Ranjbar-Karimi ◽  
Alireza Poorfreidoni
Keyword(s):  
Antibacterial Activity ◽  
Chemical Structure ◽  
Side Chain ◽  
Gram Negative Bacteria ◽  
Pyridine Derivatives ◽  
Positive Bacterium ◽  
Gram Positive ◽  
In Vitro Antibacterial Activity ◽  
Ft Ir

AbstractA series of hybrid of 4-aminoquinoline and fluorinated pyridine derivatives were synthesized and their chemical structure were confirmed by 19F-NMR, 1H-NMR, 13C-NMR and FT-IR. All compounds were tested against one Gram-positive and one Gram-negative bacteria to assess their in vitro antibacterial activity. Compounds 10a, 10b, 11a and 12b showed moderate antibacterial activity against Gram-positive bacterium, Staphylococcus aureus.

Oxidation studies on β-lactam antibiotics: In-vitro antimicrobial activity of the oxidized products of 3-heteroarylthiomethyl-ceph-3-ems

1991 ◽  
Vol 56 (11) ◽  
pp. 2362-2372 ◽  
Author(s):  
Rajeshwar Singh ◽  
Maya P. Singh ◽  
Ronald G. Micetich
Keyword(s):  
Hydrogen Peroxide ◽  
Antimicrobial Activity ◽  
Antibacterial Activity ◽  
Acetic Acid ◽  
Side Chain ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
In Vitro Antimicrobial Activity ◽  
Oxidized Products

Various products from the oxidation of 3-heteroarylthiomethyl-ceph-3-ems using m-chloroperbenzoic acid (m-CPBA) and hydrogen peroxide in acetic acid in varying stoichiometric ratios have been isolated, identified and their in vitro antimicrobial activity determined. The oxidized compounds with the 2-aminothiazol-4-yl-(Z)-2-methoxyiminoacetamido side chain showed better antibacterial activity against various Gram negative bacteria compared to the unoxidized compounds.

Structure─activity relationships in semi-synthetic penicillins

1971 ◽  
Vol 179 (1057) ◽  
pp. 357-367 ◽  
Keyword(s):  
Antibacterial Activity ◽  
Chemical Nature ◽  
Side Chain ◽  
Structural Variations ◽  
Present Survey ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Large Numbers ◽  
The Relationship

Investigation of the relationship between the antibacterial activity of penicillins and the chemical nature of the side chain began in earnest in 1957, when the isolation of 6-aminopenicillanic acid (6-APA) made possible the preparation of large numbers of N -substituted derivatives. Since that time some 1800 different penicillins have been prepared and studied in Beecham Research Laboratories, and the number examined throughout the world must amount to several thousands. The purpose of the present survey is to try to summarize the general patterns of structure-activity relationships which have emerged from these studies. 6-APA itself has only a low order of antibacterial activity, and the same applies to derivatives in which the amino group at position 6 is substituted by radicals other than acyl groups (figure 1). Hence it soon became clear that no advantage was to be gained from such considerable structural variations, and efforts were concentrated on preparing true penicillins containing acyl side-chains. Virtually all of these show considerable activity in vitro against at least some bacteria, but the spectrum of activity varies widely.

scholarly journals Characterization of 1 alpha-hydroxylation of vitamin D3 sterols by cultured alveolar macrophages from patients with sarcoidosis.

1985 ◽  
Vol 161 (4) ◽  
pp. 755-765 ◽  
Author(s):  
J S Adams ◽  
M A Gacad
Keyword(s):  
Vitamin D3 ◽  
Alveolar Macrophages ◽  
Hydroxyl Group ◽  
Side Chain ◽  
Dihydroxyvitamin D3 ◽  
Naturally Occurring ◽  
Hydroxylation Reaction ◽  
High Concentrations

We investigated the 1 alpha-hydroxylation of vitamin D3 sterols by cultured pulmonary alveolar macrophages (PAM) from patients with sarcoidosis with or without clinically abnormal calcium homeostasis. Like the naturally occurring renal 1 alpha-hydroxylase, the PAM 1 alpha-hydroxylation reaction exhibited a high affinity for 25-hydroxyvitamin D3 (25-OH-D3) and a preference for substrates containing a 25-hydroxyl group in the side chain of the sterol. Unlike the renal enzyme, the PAM 1 alpha-hydroxylating mechanism was not accompanied by 24-hydroxylating activity, even after preincubation with 75 nM 1,25-dihydroxyvitamin D3 [1,25-(OH)2-D3] or exposure to high concentrations of substrate (500 nM 25-OH-D3). The PAM 25-OH-D3-1 alpha-hydroxylation reaction was stimulated by gamma interferon and inhibited by exposure to the glucocorticoid dexamethasone. The characteristics of the PAM hydroxylation process in vitro appear to reflect the efficiency of the extrarenal production of 1,25-(OH)2-D3 and the therapeutic efficacy of glucocorticoids in patients with sarcoidosis and disordered calcium metabolism.

Synthesis and Activity of Some Antimalarial Bisquinolinemethanols

1997 ◽  
Vol 50 (11) ◽  
pp. 1091 ◽  
Author(s):  
Alan F. Cowman, ◽  
Leslie W. Deady, ◽  
Eric Deharo, ◽  
José Desneves ◽  
Leann Tilley
Keyword(s):  
Plasmodium Falciparum ◽  
Resistant Strain ◽  
Cinchona Alkaloids ◽  
Cross Resistance ◽  
Side Chain ◽  
Highly Active ◽  
New Type ◽  
Resistant Strains ◽  
Further Development

A new type of bisquinoline antimalarial, containing the basic side chain of the cinchona alkaloids, has been evaluated. Five bis ethers, from 10,11-dihydrocupreine linked through the 6′-hydroxy group by -(CH2)2n- bridges (n = 2-5) (series A), and six bis amides, from 8′-amino-10,11-dihydrocinchonidine linked by -CO(CH2)2nCO- bridges (n = 1-6) (series B), were synthesized and screened against chloroquine-sensitive and -resistant strains and a mefloquine-resistant strain of Plasmodium falciparum in vitro. Two analogues of series B (n= 4; 5), with a 2-(dibutylamino)-1-hydroxyethyl side chain (series C), were also included. Compounds within series A were generally least active. Among the rest were compounds as active as mefloquine, with diminished cross-resistance to the mefloquine-resistant strain. The most potent (series B, n = 4) was highly active against chloroquine-sensitive, chloroquine-resistant and mefloquine-resistant parasites. Invivo testing, however, showed the compound to be too toxic for further development

STEROID TRANSFORMATIONS IN VITRO BY TESTICULAR TISSUE FROM TWO CASES OF TESTICULAR FEMINISATION

1965 ◽  
Vol 49 (2) ◽  
pp. 177-192 ◽  
Author(s):  
R. Neher ◽  
F. W. Kahnt ◽  
G. D. Roversi ◽  
A. Bompiani
Keyword(s):  
Qualitative Difference ◽  
Testicular Tissue ◽  
Hydroxyl Group ◽  
Side Chain ◽  
Ample Evidence ◽  
Adenoma Tissue ◽  
Testicular Feminisation ◽  
Transformation Pattern

ABSTRACT Cryptorchid testicular and testicular adenoma tissue obtained from two patients with the testicular feminisation syndrome was incubated with 3Hor 14C-labelled pregnenolone, 17-hydroxy-pregnenolone, progesterone and androstenedione. In the tissue of both patients a similar steroid transformation pattern was observed. There was abundant biosynthesis of testosterone from androstenedione but rather little from the other precursors. Oestrone and oestradiol were formed only from androstenedione. There is ample evidence of both 17-hydroxylation and side-chain splitting, in particular with the δ5-precursors. From the ratio of the δ5- and δ4-steroids identified, it is concluded that there was, however, little dehydrogenation of the 3β-hydroxyl group. Though there seems to be no qualitative difference as compared with what is known about the possible pathways in testicular tissue from various species, our findings contrast to some extent with those reported previously by other investigators in a few cases of testicular feminisation. The possible role of anti-androgens is discussed.

scholarly journals Improvement of antibacterial efficacy using antibiotic encapsulated silica-containing redox nanoparticles

2021 ◽  
Vol 24 (1) ◽  
pp. 1854-1861
Author(s):  
Han Ngoc Tran ◽  
Nhu-Thuy Trinh ◽  
Hoai-Ngan Thien Pham ◽  
Hanh Thi Ngoc Nguyen ◽  
Vong Binh Long
Keyword(s):  
Antibacterial Activity ◽  
Nitroxide Radical ◽  
Antibacterial Activities ◽  
Diffusion Method ◽  
Side Chain ◽  
Oxygen Species ◽  
E Coli ◽  
Redox Nanoparticle ◽  
Average Size

Purpose: Improving solubility and antibacterial efficiency of cephalothin by using silica-containing redox nanoparticle (siRNP) as a system to encapsulate and deliver this hydrophobic antibiotic. Methods: siRNP was synthesized by assembling amphiphilic block copolymers possessing a reactive oxygen species scavenging nitroxide radical and drug absorptive silica moieties in a hydrophobic side chain. Cephalothin, a hydrophobic antibiotic, was encapsulated into siRNP (cephalothin@siRNP) by mixing and dialysis methods. Antibacterial activity of cephalothin@siRNP against Staphylococcus aureus (S. aureus) và Escherichia coli (E. coli) was evaluated by the agar diffusion method. Results: The average size of siRNP and cephalothin@siRNP was 43.83 nm and 50.15 nm, respectively. After encapsulation in siRNP, the solubility of cephalothin was improved compared to cephalothin in an aqueous solution. The result showed that in vitro antibacterial activities of cephalothin and cephalothin@siRNP had no statistical difference after 24 h incubation on agar plates on both S. aureus and E. coli. However, after an extended incubation time, regrowth of E. coli colonies in the inhibitory zone was found in cephalothin treated plate. Interestingly, E. coli regrowth was significantly reduced in plates treated with cephalothin@siRNP. Conclusion: In this study, siRNP successfully encapsulated cephalothin and enhanced the solubility of this drug. The antibacterial activity of cephalothin is prolonged when encapsulated in siRNP, which suppressed the reccurrence of E. coli colonies. Cephalothin@siRNP has the potential to inhibit antibiotic resistance.

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